Proc Natl Acad Sci U S A
April 2024
Clearance of serotonin (5-hydroxytryptamine, 5-HT) from the synaptic cleft after neuronal signaling is mediated by serotonin transporter (SERT), which couples this process to the movement of a Na ion down its chemical gradient. After release of 5-HT and Na into the cytoplasm, the transporter faces a rate-limiting challenge of resetting its conformation to be primed again for 5-HT and Na binding. Early studies of vesicles containing native SERT revealed that K gradients can provide an additional driving force, via K antiport.
View Article and Find Full Text PDFA new class of extragalactic astronomical sources discovered in 2021, named odd radio circles (ORCs), are large rings of faint, diffuse radio continuum emission spanning approximately 1 arcminute on the sky. Galaxies at the centres of several ORCs have photometric redshifts of z ≃ 0.3-0.
View Article and Find Full Text PDFMephedrone (4-methylmethcathinone) is a cathinone derivative that is recreationally consumed for its energizing and empathogenic effects. The stimulating properties are believed to arise from the ability of mephedrone to interact with the high-affinity transporters for dopamine (DA) (DAT) and norepinephrine (NET), whereas the entactogenic effect presumably relies on its activity at the serotonin (5-HT) transporter (SERT). Early studies found that mephedrone acts as a releaser at NET, DAT and SERT, and thus promotes efflux of the respective monoamines.
View Article and Find Full Text PDFThe serotonin transporter (SERT) removes synaptic serotonin and is the target of anti-depressant drugs. SERT adopts three conformations: outward-open, occluded, and inward-open. All known inhibitors target the outward-open state except ibogaine, which has unusual anti-depressant and substance-withdrawal effects, and stabilizes the inward-open conformation.
View Article and Find Full Text PDFBaruch Kanner and this author have had parallel careers investigating neurotransmitter transporters. At multiple times during their careers, they have found themselves collaborating or competing, but always learning from each other. This commentary elaborates on the interactions between the Kanner and Rudnick laboratories, with a focus on transporters in the Neurotransmitter: Sodium Symporter (NSS) family of amino acid and amine transporters.
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